Early detection of cardiac allograft rejection with proton nuclear magnetic resonance

No reliable, noninvasive technique is currently available for the early detection of cardiac transplant rejection. In this study, pulse nuclear magnetic resonance (NMR) spectroscopy was used (20 MHz) to detect cardiac allograft rejection in rats. Proton spin-lattice relaxation time (T1), proton spin-spin relaxation time (T2), and water content were measured in both recipient and donor hearts at 2, 4, 6, and 8 days after transplantation. Pathologic specimens were scored on a 0 to 4+ scale of increasing evidence of rejection by light microscopy. Three kinds of heterotopic transplants were performed for a total of 90: (1) Lewis rats received Lewis rat isografts, (2) Lewis rats received Brown Norway rat allografts, and (3) Lewis rats received cyclosporin A-treated allografts (15 mg/kg/day). T1 in group 2 was significantly higher than that in group 1 as early as day 2 (670 + 25 vs 616 + 11 msec, p less than .001), when histologic scores were not different. T2 in group 2 was also higher than that in group 1 (48.0 +/- 5.0 vs 41.1 +/- 2.6, p less than .005). T1 and T2 in group 2 increased from day 4 and correlated well with the water content of the hearts (r = .70 and r = .75, respectively). Cyclosporin A completely suppressed the increase of T1 and T2 in group 2. Treatment with cyclosporin also suppressed the histologic rejection scores. Our data suggest that proton relaxation time measurement may be a sensitive technique for detecting the onset of rejection and examining the therapeutic effects of cyclosporin. NMR imaging, which highlights T1 and T2 separately, should provide a sensitive noninvasive means of assessing myocardial graft rejection.